PROJECT SUMMARY Recent advances in science and technology are now making tackling of rare and undiagnosed disorders possible. By utilizing these advances, along with scientific and clinical expertise, the Undiagnosed Disease Network (UDN) promises improvement in the lives of individuals and their families affected with undiagnosed disorders. To benefit from this effort, the nation as a whole, especially the rich and rapidly increasing diversity of the US population must be taken into account. With its longstanding excellence in clinical care and research in South Florida, University of Miami is in an unsurpassed position to be a part of the UDN. We propose to create the Clinical Site-Miami (CS-Miami), which will recruit, evaluate, and provide data from participants with undiagnosed disorders. While we will be open to all participants from any location, we will specifically focus on South Florida. The diverse population of South Florida includes Hispanics from the Caribbean (e.g. Cuba, Puerto Rico and the Dominican Republic), Mexico, South and Central America, Caribbean born blacks, Jews and others from all over the world. Many of these minorities are recent immigrants whose original populations are ideal for the occurrence of rare diseases due to isolation, inbreeding, and founder effects. Our Clinical and Translational Science Institute (CTSI) is the only member of the national CTSA consortium co-funded by the National Institute on Minority Health and Health Disparities (NIMHD) to specifically focus on the health of underrepresented minorities. To represent the minority populations, we are one of the recruitment sites for NIH`s AllofUs Precision Medicine Initiative, again, with a focus of enrolling >50% of minority participants. We will build CS-Miami upon existing expertise in community engagement, electronic medical records, biorepositories, phenotypic delineation of rare diseases, characterization of their underlying biology, and access to a large collaboration network. Specific aims will be to 1) recruitment, enroll, and engage minorities into CS-Miami; 2) characterize rare and undiagnosed disease phenotypes; 3) to reach a diagnosis via collaborative analysis of standard data. Our team's combined expertise in clinical assessment, patient engagement, informatics, ethics and genomics will provide the requisite oversight and structure to ensure we meet our stated goals.